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Pregnant women with twins and a short cervical length (CL) are at greater risk of preterm birth (PTB). The comparative efficacy of cervical cerclage and cervical pessary with or without additional progesterone to prevent PTB is unknown. We aimed to assess, in women with twin pregnancies and a short CL, the effectiveness of cerclage versus pessary and the additional treatment with 400 mg vaginal progesterone versus no progesterone in preventing PTB. This multicenter, two-by-two factorial randomised trial was conducted in 2 hospitals in Ho Chi Minh City, Vietnam. Asymptomatic women with twin pregnancies and a CL ≤28 mm at 16 to 22 gestational weeks were recruited. Between March 2019 and July 2023, we randomised 219 participants (64.4% of the planned sample size) to cerclage plus progesterone (n = 55), Arabin pessary plus progesterone (n = 56), cerclage alone (n = 54) or Arabin pessary alone (n = 54). Primary outcome was any PTB <34 weeks. Following the second interim analysis, the study was terminated due to significantly lower rates of perinatal deaths and deliveries <28 weeks in the cerclage group. The primary outcome occurred in 20 (19.8%) participants receiving cerclage versus 20 (19%) participants receiving pessary (relative risk [RR] 1.04; 95% confidence interval [CI], 0.60 to 1.8). Delivery <28 weeks occurred in 1% versus 8.6% (RR 0.12; 95% CI, 0.01 to 0.52) and perinatal death occurred in 1% versus 5.8% (RR 0.17; 95% CI, 0.05 to 0.62) in the cerclage group and the pessary group, respectively. However, PTB <24 weeks, <32 weeks, and other neonatal outcomes were not significantly different between the 2 groups. For maternal side effects, vaginal discharge was significantly less frequent in the cerclage group. In participants allocated to progesterone, PTB <34 weeks occurred in 19 (18.4%) versus 21 (20.4%) participants who did not have progesterone (RR 0.90; 95% CI, 0.52 to 1.6). In this prematurely halted study on pregnant women with twins and a CL ≤28 mm, cerclage and cervical pessary were comparably effective on PTB <34 weeks prevention. However, compared to pessary, cerclage was associated with significantly lower rates of PTB <28 weeks and perinatal mortality. ClinicalTrials.gov Registration: NCT03863613 (https://clinicaltrials.gov/study/NCT03863613).

Computable general equilibrium (CGE) models are a standard tool for policy analysis and forecasts of economic growth. Unfortunately, due to computational constraints, many CGE models are dimensionally small, aggregating countries into an often limited set of regions or using assumptions such as static price‐level expectations, where next period's price is conditional only on current or past prices. This is a concern for climate change modeling, since the effects of global warming by country, in a fully disaggregated and global trade model, are needed, and the known future effects of global warming should be included in forward‐looking forecasts for prices and profitability. This work extends a large dimensional intertemporal CGE trade model to account for the various effects of global warming (e.g., loss in agricultural productivity, sea level rise, and health effects) on Gross Domestic Product (GDP) growth and levels for 139 countries, by decade and over the long term, where producers look forward and adjust price expectations and capital stocks to account for future climate effects. The potential economic gains from complying with the Paris Accord are also estimated, showing that even with a limited set of possible damages from global warming, these gains are substantial. For example, with the comparative case of Representative Concentration Pathway 8.5 (4°C), the global gains from complying with the 2°C target (Representative Concentration Pathway 4.5) are approximately US $17,489 billion per year in the long run (year 2100). The relative damages from not complying to Sub‐Sahara Africa, India, and Southeast Asia, across all temperature ranges, are especially severe. Plain Language Summary This work shows considerable global economic gains from complying with the Paris Climate Accord for 139 countries. For example, with the comparative case of a temperature increase of four degrees, the global gains from complying with the 2° target are approximately US$ 17,489 billion per year in the long run (year 2100). The relative damages from not complying to Sub‐Sahara Africa, India, and Southeast Asia are especially severe. Key Points The global economic gains from complying with the Paris Climate Accord are shown to be substantial across 139 countries With the comparative case of RCP8.5 (4°C), the global gains from complying with the 2°C target (RCP4.5) are US$17,489 billion per year The relative damages from not complying with the 2°C target to Sub‐Sahara Africa, India, and Southeast Asia are especially severe

Antisense oligonucleotides (ASOs) bind sequence specifically to the target RNA and modulate protein expression through several different mechanisms. The ASO field is an emerging area of drug development that targets the disease source at the RNA level and offers a promising alternative to therapies targeting downstream processes. To translate ASO-based therapies into a clinical success, it is crucial to overcome the challenges associated with off-target side effects and insufficient biological activity. In this regard, several chemical modifications and diverse delivery strategies have been explored. In this review, we systematically discuss the chemical modifications, mechanism of action, and optimized delivery strategies of several different classes of ASOs. Further, we highlight the recent advances made in development of ASO-based drugs with a focus on drugs that are approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for clinical applications. We also discuss various promising ASO-based drug candidates in the clinical trials, and the outstanding opportunity of emerging microRNA as a viable therapeutic target for future ASO-based therapies.

According to a review of numerous publications and scientific reports, the effects of urbanization on urban climate are of greatest concern. This study aims to evaluate the impact of urbanization focusing on population growth on precipitation trends in 11 provinces across Vietnam during the period 2008–2018 by identifying the relationship between population growth and precipitation change. Regression analysis is used to determine the trends of precipitation and population growth. Precipitation maps and graphs show the overall precipitation trends, changes, and patterns in past decades. Overall, population growth tends to correlate with precipitation change trends. Furthermore, the type of region groups (countryside region, small city, or medium city) also plays a crucial role in determining the magnitude of the change in precipitation trends for each region. This further lends credibility to the notion that urbanization contributes to changes in precipitation trends.

In 2017, Chicago’s Rush University System for Health adopted an anchor strategy to leverage its position as a large business in addressing social drivers of population health. The strategy offers an evolving case study.

Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells. Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in association with melanocyte inducing transcription factor (MITF) expression levels. We established a mouse melanoma model for deleting Stat3 in melanocytes with specific expression of human hyperactive NRAS Q61K in an Ink4a -deficient background, two frequent driver mutations in human melanoma. Mice devoid of Stat3 showed early disease onset with higher proliferation in primary tumors, but displayed significantly diminished lung, brain, and liver metastases. Whole-genome expression profiling of tumor-derived cells also showed a reduced invasion phenotype, which was further corroborated by 3D melanoma model analysis. Notably, loss or knockdown of STAT3 in mouse or human cells resulted in the upregulation of MITF and induction of cell proliferation. Mechanistically we show that STAT3-induced CAAT Box Enhancer Binding Protein ( CEBP) expression was sufficient to suppress MITF transcription. Epigenetic analysis by ATAC-seq confirmed that CEBPa/b binding to the MITF enhancer region silenced the MITF locus. Finally, by classification of patient-derived melanoma samples, we show that STAT3 and MITF act antagonistically and hence contribute differentially to melanoma progression. We conclude that STAT3 is a driver of the metastatic process in melanoma and able to antagonize MITF via direct induction of CEBP family member transcription.

Inclusive approaches have been applied in many areas, including human resources, international development, urban planning, and innovation. This paper is a systematic literature review to describe the usage trends, scope, and nature of the inclusive approach in the climate change adaptation (CCA) context. We developed search algorithms, explicit selection criteria, and a coding questionnaire, which we used to review a total of 106 peer-reviewed articles, 145 grey literature documents, and 67 national communications to the United Nations Framework Convention on Climate Change (UNFCCC); 318 documents were reviewed in total. Quantitatively, the methodology reveals a slight increase in usage, with a focus on non-Annex 1 countries, gender issues, and capacity building. Qualitatively, we arranged the key insights into the following three categories: (1) inclusion in who or what adapts; (2) motivating inclusive processes; and (3) anticipated outcomes of inclusive CCA. We conclude, with the observation, that many issues also apply to Annex 1 countries. We also argue that the common language nature of the word ‘inclusive’ makes it applicable to other CCA-relevant contexts, including government subsidies, science policy, knowledge integration and mobilization, performance measurement, and the breadth of the moral circle that a society should adopt.

Landslides, which can occur due to earthquakes and heavy rainfall, pose significant challenges across large areas. To effectively manage these disasters, it is crucial to have fast and reliable automatic detection methods for mapping landslides. In recent years, deep learning methods, particularly convolutional neural and fully convolutional networks, have been successfully applied to various fields, including landslide detection, with remarkable accuracy and high reliability. However, most of these models achieved high detection performance based on high-resolution satellite images. In this research, we introduce a modified Residual U-Net combined with the Convolutional Block Attention Module, a deep learning method, for automatic landslide mapping. The proposed method is trained and assessed using freely available data sets acquired from Sentinel-2 sensors, digital elevation models, and slope data from ALOS PALSAR with a spatial resolution of 10 m. Compared to the original ResU-Net model, the proposed architecture achieved higher accuracy, with the F1-score improving by 9.1% for the landslide class. Additionally, it offers a lower computational cost, with 1.38 giga multiply-accumulate operations per second (GMACS) needed to execute the model compared to 2.68 GMACS in the original model. The source code is available at https://github.com/manhhv87/LandSlideMapping.git .

Cyperus amuricus (Cyperaceae) has exhibited potential anticancer activity against hepatocellular carcinoma (HCC), yet its molecular mechanisms and phytoconstituent interactions with oncogenic pathways remain underexplored. This study integrates in vitro cytotoxicity assays and molecular docking to evaluate the effects of C. amuricus fractionated extracts on HCC, focusing on PI3K/AKT/mTOR signaling axis. The ethyl acetate (EA) fraction selectively inhibited HepG2 cell proliferation (IC 50 = 159.76 µg/mL) with minimal toxicity to normal fibroblasts. Apoptotic features—cell shrinkage, membrane blebbing, nuclear condensation, and DNA fragmentation—were confirmed through DAPI staining and gel electrophoresis. Western blot analysis revealed dose-dependent suppression of phosphorylated Akt and p70S6K, indicating pathway inhibition. Molecular docking identified strong binding affinities between Cyperaceae-derived compounds and PI3K/AKT/mTOR targets, with luteolin 7-O-β-D-glucuronopyranoside-6″-methyl ester blocked PI3K activation, vitexin bound AKT’s allosteric site, and digitoxin targeted mTOR’s ATP-binding pocket, showing comparable binding energies to reference ligands. These findings suggest C. amuricus as a promising candidate for natural product-based HCC therapy.

This paper investigates the performance of hybrid radio frequency/free space optical (RF/FSO) systems combined with non-orthogonal multiple access communications technology. We examine a scenario where the source and destination are separated by a large distance, with no direct link between them. The relay, denoted R, operates using the decode-and-forward (DF) protocol. Under the DF relaying scheme, the relay employs successive interference cancellation (SIC). In this setup, the FSO link from the source to the relay follows a Gamma-Gamma distribution, while the RF link from the relay to multiple users follow a Nakagami- m distribution. Based on this system model, we analyze the outage probability (OP). Our findings indicate a direct relationship between SIC and OP performance: the higher the SIC capability, the more effective the system. In addition, the system’s performance is dependent on the parameters of the FSO channel. Finally, Monte Carlo simulations are presented to further validate our framework and findings.